Hyperoside ameliorates cisplatin-induced acute kidney injury by regulating the expression and function of Oat1.

IF 1.3 4区医学 Q4 PHARMACOLOGY & PHARMACY

Xenobiotica Pub Date : 2023-12-01 Epub Date: 2023-11-26 DOI:10.1080/00498254.2023.2270046

Wenjing Yuan, Shanshan Kou, Ying Ma, Yusi Qian, Xinyu Li, Yuanyuan Chai, Zhenzhou Jiang, Luyong Zhang, Lixin Sun, Xin Huang

{"title":"Hyperoside ameliorates cisplatin-induced acute kidney injury by regulating the expression and function of Oat1.","authors":"Wenjing Yuan, Shanshan Kou, Ying Ma, Yusi Qian, Xinyu Li, Yuanyuan Chai, Zhenzhou Jiang, Luyong Zhang, Lixin Sun, Xin Huang","doi":"10.1080/00498254.2023.2270046","DOIUrl":null,"url":null,"abstract":"Cisplatin is a widely used chemotherapeutic agent to treat solid tumours in clinics. However, cisplatin-induced acute kidney injury (AKI) limits its clinical application. This study investigated the effect of hyperoside (a flavonol glycoside compound) on regulating AKI.The model of cisplatin-induced AKI was established, and hyperoside was preadministered to investigate its effect on improving kidney injury.Hyperoside ameliorated renal pathological damage, reduced the accumulation of SCr, BUN, Kim-1 and indoxyl sulphate in vivo, increased the excretion of indoxyl sulphate into the urine, and upregulated the expression of renal organic anion transporter 1 (Oat1). Moreover, evaluation of rat kidney slices demonstrated that hyperoside promoted the uptake of PAH (p-aminohippurate, the Oat1 substrate), which was confirmed by transient over-expression of OAT1 in HEK-293T cells. Additionally, hyperoside upregulated the mRNA expression of Oat1 upstream regulators hepatocyte nuclear factor-1α (HNF-1α) and pregnane X receptor (PXR).These findings indicated hyperoside could protect against cisplatin-induced AKI by promoting indoxyl sulphate excretion through regulating the expression and function of Oat1, suggesting hyperoside may offer a potential tactic for cisplatin-induced AKI treatment.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"559-571"},"PeriodicalIF":1.3000,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Xenobiotica","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/00498254.2023.2270046","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/11/26 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}

引用次数: 0

Abstract

Cisplatin is a widely used chemotherapeutic agent to treat solid tumours in clinics. However, cisplatin-induced acute kidney injury (AKI) limits its clinical application. This study investigated the effect of hyperoside (a flavonol glycoside compound) on regulating AKI.The model of cisplatin-induced AKI was established, and hyperoside was preadministered to investigate its effect on improving kidney injury.Hyperoside ameliorated renal pathological damage, reduced the accumulation of SCr, BUN, Kim-1 and indoxyl sulphate in vivo, increased the excretion of indoxyl sulphate into the urine, and upregulated the expression of renal organic anion transporter 1 (Oat1). Moreover, evaluation of rat kidney slices demonstrated that hyperoside promoted the uptake of PAH (p-aminohippurate, the Oat1 substrate), which was confirmed by transient over-expression of OAT1 in HEK-293T cells. Additionally, hyperoside upregulated the mRNA expression of Oat1 upstream regulators hepatocyte nuclear factor-1α (HNF-1α) and pregnane X receptor (PXR).These findings indicated hyperoside could protect against cisplatin-induced AKI by promoting indoxyl sulphate excretion through regulating the expression and function of Oat1, suggesting hyperoside may offer a potential tactic for cisplatin-induced AKI treatment.

查看原文本刊更多论文

金丝桃苷通过调节Oat1的表达和功能改善顺铂诱导的急性肾损伤。

顺铂是临床上广泛使用的治疗实体瘤的化疗药物。然而，顺铂诱导的急性肾损伤（AKI）限制了其临床应用。本研究观察了金丝桃苷对急性肾损伤的调节作用，建立了顺铂诱导的急性肾损伤模型，并对金丝桃苷进行预处理，观察其改善肾损伤的作用。金丝桃苷改善肾脏病理损伤，减少体内SCr、BUN、Kim-1和硫酸吲哚酚的积累，增加硫酸吲哚酚向尿液中的排泄，并上调肾脏有机阴离子转运蛋白1（Oat1）的表达。此外，对大鼠肾切片的评估表明，金丝桃苷促进了PAH（对氨基马齿苋酸酯，Oat1底物）的摄取，这通过HEK-293T细胞中Oat1的瞬时过表达得到了证实。此外，金丝桃苷上调了Oat1上游调节因子肝细胞核因子-1α（HNF-1α）和孕烷X受体（PXR）的mRNA表达。这些发现表明金丝桃苷可以通过调节Oat1的表达和功能来促进硫酸吲哚酚的排泄，从而保护顺铂诱导的AKI，提示金丝桃苷可能为顺铂诱导的AKI治疗提供一种潜在的策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Xenobiotica 医学-毒理学

CiteScore

3.80

自引率

5.60%

发文量

审稿时长

2 months

期刊介绍： Xenobiotica covers seven main areas, including:General Xenobiochemistry, including in vitro studies concerned with the metabolism, disposition and excretion of drugs, and other xenobiotics, as well as the structure, function and regulation of associated enzymesClinical Pharmacokinetics and Metabolism, covering the pharmacokinetics and absorption, distribution, metabolism and excretion of drugs and other xenobiotics in manAnimal Pharmacokinetics and Metabolism, covering the pharmacokinetics, and absorption, distribution, metabolism and excretion of drugs and other xenobiotics in animalsPharmacogenetics, defined as the identification and functional characterisation of polymorphic genes that encode xenobiotic metabolising enzymes and transporters that may result in altered enzymatic, cellular and clinical responses to xenobioticsMolecular Toxicology, concerning the mechanisms of toxicity and the study of toxicology of xenobiotics at the molecular levelXenobiotic Transporters, concerned with all aspects of the carrier proteins involved in the movement of xenobiotics into and out of cells, and their impact on pharmacokinetic behaviour in animals and manTopics in Xenobiochemistry, in the form of reviews and commentaries are primarily intended to be a critical analysis of the issue, wherein the author offers opinions on the relevance of data or of a particular experimental approach or methodology